Emergence of four cases of KPC-2 and KPC-3-carrying Klebsiella pneumoniae introduced to Switzerland, 2009-10.

We report four epidemiologically unrelated cases of KPC-carrying Klebsiella pneumoniae identified in Switzerland between May 2009 and November 2010. Three cases were transferred from Italy (two KPC-3, one KPC-2) and one from Greece (KPC-2). Resistance to colistin and doxycycline emerged in one KPC-3-carrying K. pneumoniae strain during therapy. These results demonstrate ongoing dissemination of KPC throughout Europe. Rapid and reliable identification of KPC and implementation of control measures is essential to limit spread.

An oestradiol-linked nitrosourea and site-directed chemotherapy in mammary carcinoma.

The half-life, peak concentration, peak accumulation and tissue availability of the DNA-crosslinking nitrosourea 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine (CNC-alanine) and its oestradiol-linked derivate (CNC-alanine-oestradiol-17-ester) were studied in liver, lung, spleen, uterus and mammary carcinomas in female Sprague-Dawley rats with chemically induced mammary carcinomas. Compared with CNC-alanine, the ester had a longer half-life, higher peak concentration, increased peak accumulation and enhanced tissue availability in all tissues. In oestradiol receptor positive mammary carcinomas, the oestradiol-linked drug showed a 2 times higher peak concentration, a 5 times longer half-life, a 10 times increased peak accumulation and a 20 times greater tissue availability compared with CNC-alanine. Oestradiol-linked nitrosoureas may offer new perspectives for site-directed chemotherapy of oestradiol receptor positive breast cancer.

The pharmacokinetic model and distribution pattern of new sexual-steroid-hormone-linked anticancer agents.

Sexual-steroid-hormone-linked anticancer agents are a new group of cytotoxic drugs designed for a site-directed chemotherapy of tumors containing sexual steroid hormone receptors. The hormone (e.g. estradiol or testosterone) should act as a carrier that leads to a preferential receptor-mediated drug accumulation in hormone-receptor-positive tumors (such as mammary carcinomas and prostatic cancer). In several preclinical therapeutic studies of sexual-hormone-receptor-positive breast cancer, for instance, conjugates of 2-chloroethyl-carbamoyl-L-alanine linked to estradiol or dihydrotestosterone showed, in comparison to the unlinked single agent, a significantly higher antineoplastic activity and a clearly lower systemic toxicity. But there is still only limited knowledge about the pharmacokinetic properties and the mode of action of these new drugs. For this reason in the present article a more comprehensive pharmacokinetic model and the pattern of distribution of new sexual-steroid-hormone-linked anticancer agents have been described.

Hexadecylphosphocholine differs from conventional cytostatic agents.

Alkylphosphocholines, and especially their main representative hexadecylphosphocholine (HPC), show high anticancer activity in methylnitrosourea (MNU)-induced autochthonous rat mammary carcinoma. The regression of MNU-induced rat mammary carcinoma during HPC treatment can be evaluated by computed tomography and sonography. This allows a noninvasive monitoring of therapy in vivo (tumor size, morphology, and blood supply). Both diagnostic modalities can show a rapid concentric decrease in tumor volume as well as the appearance of cystic, scarry, and necrotic areas in the tumor tissue as a result of HPC treatment. In addition, prior to, during and after therapy tumor perfusion can be assessed by color Doppler sonography in vivo. A more than 4-fold difference in HPC efficacy was observed when the colony growth of explanted MNU-induced mammary carcinoma cells was measured in the methylcellulose colony assay (IC50 = 180 mumol HPC/l) and the Hamburger Salmon colony assay (IC50 = 740 mumol HPC/l). In the latter assay, growth of concomitantly seeded untransformed cells, especially of fibroblasts, is much lower than in the methyl-cellulose colony assay. We therefore assume that the antitumor efficacy of HPC against MNU-induced mammary carcinoma is enhanced by neighboring cells such as fibroblasts. Cell culture experiments with the three MNU-induced rat mammary carcinoma cell clones 1-C-2, 1-C-30, and 1-C-32 revealed IC50 values in the range of 50-70 mumol HPC/l. The volume of 1-C-2 cells increased up to 4-fold after 72 h of permanent exposure to 100 mumol HPC/l, a concentration that completely inhibited proliferation of tumor cell numbers without being cytotoxic. Nucleotide triphosphate levels dropped significantly after 24 h and were slowly restored in spite of continued exposure. After 72 h, they nearly reached those levels observed in plateau-phase cells. This suggests that HPC-induced growth inhibition has similarities with physiologically occurring growth arrest. Finally, replication of RNA viruses and DNA viruses was suppressed 30-fold and 7-fold, respectively, at low concentrations of HPC (12 mumol/l), which caused no or negligible growth inhibition in the virus-harboring cells, thus demonstrating specific antiviral activity of HPC. From these observations we conclude that HPC differs in many important aspects from conventional cytostatic agents and is certainly worth following-up in further investigations.

Non-contact eye-tracking on cats.

The objective of visual systems neuroscience has shifted over the past few years from determining the receptive fields of cells towards the understanding of higher level cognition in awake animals viewing natural stimuli. In experiments with awake animals it is important to control the relevant aspects of behavior. Most important for vision science is the control of the direction of gaze. Here we present Dual Purkinje eye-tracking on cats, which--as a non-contact method--brings a number of advantages. Along with the presented methods for calibration and for synchronization to off-the-shelf video presentation hardware, this method allows high precision experiments to be performed on cats freely viewing videos of natural scenes.

[The initial experiences with a new method for treating invagination: sonography-guided hydrostatic reduction]. / Erste Erfahrungen mit einer neuen Methode zur Behandlung der Invagination: die sonographisch gesteuerte hydrostatische Reposition.

During the last four months we have been treating all 15 sonographically diagnosed intussusceptions by a new method; this is based on the introduction of a saline enema under sonographic control. In 13 cases the method was successful according to imaging and clinical criteria. In two patients conservative reduction was impossible: in one patient partial resection of the ileum was necessary and in the other there was a recurrence which was reduced at operation. There were no complications. The advantages of the method are reduced radiation exposure, complete evaluation of the course of the procedure with definite criteria for success, the ability to recognise an ileo-ileal invagination and to determine the head of the intussusceptum. We can see no disadvantages compared with conventional methods. We regard this method as optimal in future for the treatment of infantile intussusceptions.

[Color Doppler ultrasound of the mediastinum. Examination technique and sectional anatomy of the image]. / Farbdopplersonographie des Mediastinums. Untersuchungstechnik und Schnittbildanatomie.

The standardized technique and typical normal findings of color-coded duplex sonography of the mediastinum are described. Anatomical structures of the sonographical presentations are explained. Important mediastinal regions, vessels and lymph nodes can be assessed sonographically. The conventional B-mode technique provides topographical orientation and is suitable for high-resolution imaging of mediastinal structures. The color-coded display of blood flow allows reliable identification of the various mediastinal vessels. The qualitative and quantitative characterization of blood flow (flow direction, flow velocity, flow quality: arterial-venous, laminar, turbulent) provides additional noninvasive information about the hemodynamics of the mediastinal vascular system.

The post-reduction donut sign.

A donut-shaped intestinal structure in the lower right abdomen, observed during abdominal ultrasound investigation following nonoperative intussusception reduction, may create a diagnostic problem concerning differentiation from a residual or recurrent intussusception or underlying small bowel disease. In 30 cases of ileocolic intussusception an abdominal ultrasound examination was performed after reduction, the success of which was proven by radiological and clinical criteria. More than half of the examinations showed an aperistaltic "donut" in the ileocecal region which was similar to the target sign commonly seen in intussusception. Differentiation was possible according to the following two criteria: first, the diameter of the donut was smaller than that of the original target sign seen in these patients. Second, the donut consisted of a broad hypoechoic rim and an echogenic center, whereas the target was normally composed of multiple concentric rings. One third of the patients showed localized thickening of the walls of the distal ileal loops which did not cause diagnostic problems. All of the suspicious intestinal structures disappeared within the first 5 days following reduction. It is our opinion that the post-reduction donut correlates with significant edema of the ileocecal valve and does not represent a mechanical lead point or persisting residual intussusception.

A new comprehensive technique of catheterisation, blood sampling, sample preparation and sample analysis by means of high-pressure liquid chromatography for pharmacokinetic studies with estradiol-linked nitrosoureas and their metabolites.

Estradiol-linked nitrosoureas are offering new perspectives in the antineoplastic chemotherapy of estradiol-receptor positive mammary carcinomas. In such a molecule estradiol has the function of a carrier which brings about a specific accumulation of the anticancer drug in estradiol-receptor containing tumor cells. However, there is only little knowledge about the pharmacokinetic behavior of this new group of anticancer agents. For that reason a new comprehensive technique of catheterisation, blood sampling, sample preparation and sample analysis with high-pressure liquid chromatography (HPLC) for preclinical pharmacokinetic studies with estradiol-linked nitrosoureas and their metabolites has been developed. N-(2-Chloroethyl)-N-nitroso-carbamoyl-L-alanine-estradiol-17-ester (CNC-alanine-estradiol-17-ester) and N-(2-chloroethyl)-N-nitroso-carbamoyl-L-alanine (CNC-alanine) were used as test compounds. The drugs were tested in female Sprague-Dawley rats with chemically induced mammary carcinomas. The laboratory animals were supplied with two catheters prior to the pharmacokinetic experiments. The blood samples were drawn from the vena cava catheter after the drug had been applied through a vena jugularis catheter. The compounds were extracted from plasma with C18 silicagel reversed phase cartridges. The clean-up technique delivered clear samples only slightly contaminated with the biological matrix. The recovery from plasma was 75 +/- 5% for the hormone-linked CNC-alanine-estradiol-17-ester and 70 +/- 5% for the unlinked CNC-alanine. The analysis was carried out by means of HPLC.(ABSTRACT TRUNCATED AT 250 WORDS)

[Comparison of computerized tomography and B-image ultrasound in imaging diagnosis of the mediastinum]. / Vergleich von Computertomographie und B-Bild-Sonographie in der bildgebenden Diagnostik des Mediastinums.

40 patients with suspected mediastinal tumors were independently examined with computed tomography (CT) and sonography. The findings were confirmed by bronchoscopy, mediastinoscopy or surgery. In the assessment of the upper and middle mediastinum, sonography reaches a high sensitivity. On the contrary, in the evaluation of the anterior and posterior mediastinum, sonography is clearly inferior to CT. 90% of the tumors demonstrated by CT could be assessed with sonography. The most frequent tumors can be diagnosed with ultrasound. The evaluation of tumors in the paravertebral and retrosternal space is limited. Sonography of the mediastinum is a noninvasive, well-reproducible and cost-effective imaging modality that provides important information in cases of unclear X-ray and CT findings. The preliminary results encourage to a more frequent use of mediastinal sonography.

New estradiol-linked nitrosoureas: can the pharmacokinetic properties help to explain the pharmacodynamic activities?

The pharmacokinetics of 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine-estradiol-17-ester (CNC-alanine-estradiol-17-ester) a new estradiol-linked anticancer drug and the unlinked DNA-crosslinking agent 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine (CNC-alanine) have been studied in methylnitrosourea-induced female Sprague-Dawley rats after equimolar intravenous and oral administration. In comparison with the unlinked single agent, the CNC-alanine-estradiol-17-ester showed a 3-fold longer halflife in plasma and a three times larger volume of distribution. The distribution after intravenous administration was nearly three times faster. The absorption after peroral administration was likewise two times faster. The bioavailability of the estradiol-linked drug was determined to be 52%. After application of CNC-alanine-estradiol-17-ester the cytostatic metabolite CNC-alanine was found, indicating the cleavage of the ester bond. CNC-alanine generated from CNC-alanine-estradiol-17-ester showed a 50% longer halflife than when applied directly. The results indicate that linking 2-chloroethyl-nitrosoureas to estradiol can result in new anticancer agents with modified properties in comparison to the unlinked single agent. The higher antineoplastic activity of the hormone-linked drug can mainly be attributed to differences in the pharmacokinetic behaviour.

[Lymphoma in childhood]. / Lymphome im Kindesalter.

Manifestation of childhood Hodgkin's disease and Non-Hodgkin's lymphoma differ, especially in the latter, from those in adults. Extranodal involvement is seen even more frequently in childhood Non-Hodgkin's lymphomas than in adults. This article reviews the radiological findings in malignant lymphomas in children, explains the differences in the manifestation of Hodgkin's lymphomas, of different subtypes and of the malignant lymphomas in adults. The problems in diagnosis of organ manifestation and special problems of diagnostic imaging procedures in children are discussed.

[Malignant lymphoma in childhood. Ultrasound diagnosis]. / Maligne Lymphome im Kindesalter. Ultraschalldiagnostik.

The sonographic diagnosis of malignant lymphoma in childhood is described. Malignant lymphomas are sonographically relatively uniform: initial enlargement of the lymph nodes and organs involved and disturbance of normal echo texture by mainly hypoechoic lesions can be found. Generally, four sonographic patterns of infiltration are described: diffuse, small nodular, large nodular and bulky type. Secondary, tumor-related or inflammatory complications (e.g. dislocation or compression of vessels, thoracic inlet syndrome, venous thrombosis, ileus, urinary retention, abscess and effusion) can be sonographically evaluated. Response to therapy correlates with normalization of size and echo texture and recovery from tumor-related complications. Differential diagnosis with ultrasound is based on the topographic distribution and echo pattern of infiltration and, with certain restrictions, on the echogenicity of lesions and perfusion feasible with Doppler sonography. The primary diagnosis has to be established histologically.

[Diagnosis of pulmonary diseases with transthoracic ultrasound]. / Diagnostik pulmonaler Erkrankungen mit transthorakaler Sonographie.

The indications or ultrasound in the evaluation of pulmonary disorders are described. Clinical applications are several lung diseases in adults and especially in children. In specific, well-defined applications, the feasibilities of ultrasound are promising. Sonography provides important additional information to chest X-ray and is even superior to CT under special circumstances. Pulmonary sonography is a useful link between conventional X-ray and more expensive cross-sectional imaging. In the evaluation of pulmonary diseases at present the potential of ultrasound is not optimally used.

Modulation of cytosolic sexual steroid receptors in autochthonous methylnitrosourea-induced rat mammary carcinoma following application of 2-chloroethylnitrosocarbamoyl-L-alanine linked to oestradiol or dihydrotestosterone.

This study concentrated on the influence of 2-chloroethylnitrosocarbamoyl-L-alanine (CNC-L-ala) linked to oestradiol (CNA-L-ala-E2) or dihydrotestosterone (CNC-L-ala-DHT) in position 17 of the respective steroid hormone on tumour growth and receptor kinetics of methylnitrosourea-induced rat mammary carcinoma. Both compounds almost completely arrested logarithmically growing mammary carcinoma of Sprague-Dawley rats: in the first week CNC-L-ala-E2 blocked the growth of these tumours by 92% compared to untreated control animals while, in animals treated with the physically equimolar mixture of CNC-L-ala and oestradiol (positive control), tumour growth was inhibited by 51% only. CNC-L-ala-DHT arrested the tumour growth in the first week by 95%, while the respective positive control (CNC-L-ala plus dihydrotestosterone) effected a growth inhibition of 71% compared to the untreated control. These results correlate well with the influence of both drugs on the cytosolic receptor content of sexual steroid hormones in the tumours. CNC-L-ala-E2 depleted the content of oestradiol receptors and kept it down for a week, while concomitantly the content of progesterone receptors increased considerably and that of androgen receptors showed a short-lived decrease. CNC-L-ala-DHT depleted androgen receptors as well as progesterone receptors. The content of androgen receptors remained low for a week, while that of progesterone receptors recovered within 8 days. The content of oestrogen receptors showed a moderate decrease.

[Malignant lymphoma. Diagnosis and after-care in adults with special reference to cross-sectional imaging]. / Maligne Lymphome. Diagnostik und Nachsorge beim Erwachsenen unter besonderer Berücksichtigung der Schnittbildverfahren.

Radiological staging continues to remain the basis of a critical therapy of malignant lymphoma. As staging system, the Ann Arbor classification with some added modification is used. Up to now, CT is the imaging study of choice for staging and follow-up of cases of lymphoma. In future however, due to the advantages of the MRI, parts of the staging will be performed by MRI only. Imaging studies provide accurate measurement of extent of nodal disease. The detection of extra-nodal disease depends on the growth pattern and on the location. Focal lesions of sufficient size can be readily detected, diffuse infiltration is often missed. Computed tomography precisely reflects pathologic changes of lung involvement, but the findings are not specific. One weakness of the imaging studies is the low detection rate of splenic and hepatic involvement. Staging of gastrointestinal lymphoma has been improved by "hydro-CT" or "Hydro-MRI".

[Measurement of the blood flow velocity in the pulmonary arteries using the magnetic resonance technique]. / Messung der Blutflussgeschwindigkeit in den Pulmonalarterien mit Hilfe der Magnetresonanztechnik.

MR blood velocity measurements were performed by the RACE technique in a plane perpendicular to the flow of the pulmonary arteries. MR findings were correlated with those of perfusion scintigraphy, Doppler US and right heart catheter (thermodilution). The ratio of MR blood flow measurements of right and left pulmonary arteries correlated well with the results of perfusion scintigraphy (RPA to LPA) and Doppler. Poor correlation was found when comparing MR blood flow measurements with right heart catheter since absolute flow measurements can be superimposed by neighboring blood vessels in complex anatomic situations.